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Azilsartan attenuates lipopolysaccharide-induced acute lung injury via the Nrf2/HO-1 signaling pathway

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Abstract

Acute lung injury (ALI) is a severe complication of sepsis and hemorrhagic shock with high morbidity. In the present study, the protective effect of Azilsartan on lipopolysaccharide (LPS)-induced ALI in mice was investigated to explore the potential therapeutic property of Azilsartan for the treatment of ALI. LPS was used to induce an ALI model in mice. Hematoxylin–eosin (HE) staining sections were then evaluated for the pathological state of lung tissues. Bronchoalveolar lavage fluid (BALF) protein concentration, wet/dry weight ratios of lung tissues, and pulmonary myeloperoxidase (MPO) activity were detected to determine the degree of pulmonary injury. The number of total cells, macrophages, and neutrophils in BALF were counted using a hemocytometer to illustrate the inflammatory cell infiltration. The lung function was monitored using a spirometer. The concentrations of interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were determined using enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated by the superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) concentrations in the lung tissue. The expressions of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined using Western blot analysis. Azilsartan therapy alleviated LPS-induced lung tissue damage, increased BALF protein concentration, lung wet to dry weight ratio, MPO activity, and macrophage and neutrophils infiltration. Also, Azilsartan ameliorated the production of inflammatory factors (IL-1β, MCP-1, and IL-8). Azilsartan ameliorated LPS-impaired lung SOD activity, the GSH concentration, and the MDA concentration. Mechanistically, Azilsartan activated the LPS-impaired Nrf2/HO-1 signaling pathway. Azilsartan therapy attenuates LPS-induced ALI via the Nrf2/HO-1 signaling pathway.

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Data availability

Experimental data are available on the reasonable request to the corresponding author.

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Funding

This study is funded by “The Training Program of Leading Talents of Pudong Health System, Shanghai (Grant/Award Number: PWRl2017-01),” “The Training Program of the Key Department of Pudong Health System, Shanghai (Grant/Award Number: PWZzk2017-18),” and “Young Medical Talents Training Program of Pudong Health Bureau of Shanghai (Grant/Award Number: PWRq2020-46).”

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Author notes

  1. Chengshi Zhang and Yunfeng Zhao contributed equally to this paper.

Authors and Affiliations

  1. Department of Respiratory, Punan Hospital, Pudong New Area, Shanghai, 200125, China

    Chengshi Zhang & Yunfeng Zhao

  2. Department of Endocrinology, Punan Hospital, No.279, Linyi Road, Pudong New Area, Shanghai, 200125, China

    Xiaorong Yang

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  1. Chengshi Zhang
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Contributions

Xiaorong Yang made substantial contributions to the conceptions of the study; Chengshi Zhang and Yunfeng Zhao contributed to the investigations and data curation; Xiaorong Yang drafted the manuscript. All the authors have read and approved the submission.

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Correspondence to Xiaorong Yang.

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Zhang, C., Zhao, Y. & Yang, X. Azilsartan attenuates lipopolysaccharide-induced acute lung injury via the Nrf2/HO-1 signaling pathway. Immunol Res 70, 97–105 (2022). https://doi.org/10.1007/s12026-021-09240-1

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